Method and apparatus for optimization of cardiac resynchronization therapy using heart sounds

ABSTRACT

A cardiac rhythm management system provides for assessment of cardiac mechanical dyssynchrony based on heart sound morphology and optimization of pacing parameters based on the effect of pacing on the cardiac mechanical dyssynchrony assessment. A degree of cardiac mechanical dyssynchrony is measured by the time delay between tricuspid valve closure and mitral valve closure and/or the time delay between pulmonary valve closure and aortic valve closure. A cardiac resynchronization therapy is optimized by determining therapy parameters to provide an approximately minimum degree of cardiac mechanical dyssynchrony by cardiac pacing.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to co-pending, commonly assigned, U.S.patent application Ser. No. 10/334,694, entitled “METHOD AND APPARATUSFOR MONITORING OF DIASTOLIC HEMODYNAMICS,” filed Dec. 30, 2002, and U.S.patent application Ser. No. 10/307,896, “PHONOCARDIOGRAPHIC IMAGE-BASEDATRIOVENTRICULAR DELAY OPTIMIZATION,” filed Dec. 2, 2002, which arehereby incorporated by reference in their entirety.

FIELD OF THE INVENTION

This document generally relates to cardiac rhythm management (CRM)systems and particularly, but not by way of limitation, to such systemsproviding for optimization of cardiac therapy using heart sounds.

BACKGROUND

The heart is the center of a person's circulatory system. It includes acomplex electromechanical system performing two major pumping functions.The heart includes four chambers: right atrium (RA), right ventricle(RV), left atrium (LA), and left ventricle (LV). The RA drawsdeoxygenated blood from organs of the body and injects it into the RVthrough the tricuspid valve. The RV pumps the deoxygenated blood to thelungs through the pulmonary valve. The blood gets oxygenated in thelungs. The LA draws oxygenated blood from the lungs and injects it intothe LV through the mitral valve. The LV pumps the oxygenated blood tothe organs of the body, through the aortic valve, to provide the organswith their metabolic needs for oxygen. These mechanical pumpingfunctions are accomplished by contractions of the myocardium (heartmuscles). In a normal heart, the sinoatrial (SA) node, the heart'snatural pacemaker, generates electrical impulses, called actionpotentials, that propagate through an electrical conduction system tovarious regions of the heart to excite myocardial tissues in theseregions. Coordinated delays in the propagations of the action potentialsin a normal electrical conduction system cause the muscles in variousregions of the heart to contract in mechanical synchrony such that thepumping functions are performed efficiently.

The normal pumping functions of the heart, indicated by the normalhemodynamic performance, require a normal electrical system to generatethe action potentials and deliver them to designated portions of themyocardium with proper timing, a normal myocardium capable ofcontracting with sufficient strength, and a normal electromechanicalassociation such that all regions of the heart are excitable by theaction potentials. A blocked or otherwise abnormal electrical conductionand/or deteriorated myocardial tissue cause dysynchronous contraction ofthe heart, resulting in poor hemodynamic performance, including adiminished blood supply to the heart and the rest of the body. Thecondition where the heart fails to pump enough blood to meet the body'smetabolic needs is known as heart failure.

Because the pumping functions are mechanical functions, the hemodynamicperformance is ultimately determined by the mechanical synchrony of theheart. For this and other reasons, there is a need for a directassessment of cardiac mechanical dyssynchrony. The assessment serves asa direct measure of efficacy for a cardiac therapy restoring the cardiacmechanical synchrony.

SUMMARY

A cardiac rhythm management (CRM) system provides for assessment ofcardiac mechanical dyssynchrony based on heart sound morphology andoptimization of pacing parameters based on the effect of pacing on thecardiac mechanical dyssynchrony assessment. A degree of cardiacmechanical dyssynchrony is measured by the time delay between tricuspidvalve closure and mitral valve closure and/or the time delay betweenpulmonary valve closure and aortic valve closure. A cardiacresynchronization therapy is optimized by determining therapy parametersto provide an approximately minimum degree of cardiac mechanicaldyssynchrony by cardiac pacing.

In one embodiment, a system for analyzing a heart includes a heart soundinput, a heart sound detector, and a computer-based heart soundmorphology analyzer. The heart sound input receives one or more signalsindicative of heart sounds. The heart sound detector detects heartsounds of at least one predetermined type. The computer-based heartsound morphology analyzer produces at least one dyssynchrony parameterindicative of a degree of cardiac mechanical dyssynchrony based onmeasurements of the detected heart sounds. The heart sound morphologyanalyzer includes a heart sound measurement module to measure one ormore parameters each based on at least one morphological feature of thedetected heart sounds. The morphological feature indicates a timeinterval between closures of a first cardiac valve and a second cardiacvalve of the heart in one cardiac cycle.

In one embodiment, a system for analyzing a heart includes animplantable system and an external system communicating with theimplantable system. The implantable system includes one or moreimplantable heart sound sensors and an implantable medical device. Theone or more implantable heart sound sensors sense one or more heartsound signals each indicative of heart sounds. The implantable medicaldevice includes an implant controller to process the one or more heartsound signals and an implant telemetry module to transmit the one ormore heart sound signals to the external system. The external systemincludes an external telemetry module to receive the one or more heartsound signals and an external controller to process the one or moreheart sound signals. The external controller includes a heart soundmorphology analyzer to produce at least one dyssynchrony parameterindicative of a degree of cardiac mechanical dyssynchrony. The heartsound morphology analyzer includes a heart sound measurement module tomeasure one or more parameters each based on at least one morphologicalfeature of heart sounds of at least one predetermined type. Themorphological feature indicates a time interval between closures of afirst cardiac valve and a second cardiac valve of a heart in one cardiaccycle.

In one embodiment, a method for operating a cardiac pacemaker isprovided. One or more heart sound signals indicative of heart sounds arereceived. Heart sounds of at least one predetermined type are detected.One or more dyssynchrony parameters each indicative of a degree ofcardiac mechanical dyssynchrony are produced based on at least onemorphological feature of the detected heart sounds by executing anautomated cardiac mechanical dyssynchrony algorithm. One or more pacingparameters for minimizing the degree of cardiac mechanical dyssynchronyare determined based on the one or more dyssynchrony parameters.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects of the invention will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof, each of which are not tobe taken in a limiting sense. The scope of the present invention isdefined by the appended claims and their equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are for illustrative purposes only and notnecessarily drawn to scale, like numerals describe similar componentsthroughout the several views. The drawings illustrate generally, by wayof example, but not by way of limitation, various embodiments discussedin the present document.

FIG. 1 is a graph illustrating a sensed heart sound signal before andafter envelope detection.

FIG. 2 is a graph illustrating heart sound signals indicative of cardiacmechanical synchrony sensed by various heart sound sensors.

FIG. 3 is a graph illustrating heart sound signals indicative of cardiacmechanical dyssynchrony sensed by various heart sound sensors.

FIG. 4 is a block diagram illustrating one embodiment of a system foroptimizing pacing parameters based on a cardiac mechanical dyssynchronyassessment.

FIG. 5 is an illustration of one embodiment of a CRM system and portionsof the environment in which the CRM system is used.

FIG. 6 is a block diagram illustrating one embodiment of a circuit ofthe CRM system.

FIG. 7 is a flow chart illustrating one embodiment of a method foroptimizing pacing parameters based on the cardiac mechanicaldyssynchrony assessment.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings which form a part hereof, and in which is shown byway of illustration specific embodiments in which the invention may bepracticed. These embodiments are described in sufficient detail toenable those skilled in the art to practice the invention, and it is tobe understood that the embodiments may be combined, or that otherembodiments may be utilized and that structural, logical and electricalchanges may be made without departing from the spirit and scope of thepresent invention. The following detailed description provides examples,and the scope of the present invention is defined by the appended claimsand their equivalents.

It should be noted that references to “an”, “one”, or “various”embodiments in this disclosure are not necessarily to the sameembodiment, and such references contemplate more than one embodiment.

This document discusses, among other things, a method and system foroptimizing therapies based on mechanical performance of the heart asindicated by heart sounds. Heart sounds, or generally energies resultedfrom the heart's mechanical vibrations, indicate the heart's mechanicalactivities, including the openings and closures of the tricuspid,pulmonary, mitral, and aortic valves. Because hemodynamic performance isultimately determined by the mechanical synchrony of the heart, heartsounds provide a direct measure of efficacy for a therapy intended torestore the heart's ability to contract in synchrony.

Throughout this document, “heart sound” includes audible and inaudiblemechanical vibrations caused by cardiac mechanical activities that canbe sensed with an accelerometer. S1 generally refers to a heart soundtype known as the “first heart sound,” or as one or more occurrences orinstances of the first heart sound, depending on the context. S2generally refers to a heart sound type known as the “second heartsound,” or as one or more occurrences or instances of the second heartsound, depending on the context. A “user” includes a physician or othercaregiver who examines and/or treats a patient using one or more of themethods and apparatuses reported in the present document.

FIG. 1 is a graph illustrating a sensed heart sound signal 100 and aprocessed heart sound signal 102 over one cardiac cycle. Both signals100 and 102 indicate S1 and S2. Sensed heart sound signal 100 representsan output of a heart sound sensor such as an accelerometer sensing theheart's mechanical vibrations or a microphone sensing audible soundoriginated from the heart. The signal is conditioned by at leastenvelope detection to produce heart sound signal 102. In the system andmethod descriptions below, a “heart sound signal” refers to either aheart sound signal as an output of a heart sound sensor, such asillustrated by signal 100, or a heart sound signal that has beenenvelope detected, such as illustrated by signal 102.

Each cardiac cycle includes a diastolic phase, during which blood fillsthe RV through the tricuspid valve and the LV through mitral valve, anda systolic phase, during which the blood are ejected from the RV throughthe pulmonary valve and the LV through the aortic valve. S1 is known tooriginate from, among other things, the mechanical vibrations associatedwith tricuspid valve closure and mitral valve closure, which start thediastolic phase. S2 is known to originate from, among other things, themechanical vibrations associated with pulmonary valve closure and aorticvalve closure, which start the systolic phase.

FIG. 2 is a graph illustrating heart sound signals indicative of cardiacmechanical synchrony sensed by various heart sound sensors over acardiac cycle. A “global” heart sound signal 202G is sensed by a singleheart sound sensor sensing heart sounds originated from the entireheart. Heart sound signal 202G indicates S1 _(G) (global S1) and S2 _(G)(global S2) for heart that contracts synchronously. S1 _(G) ismorphologically characterized by a single peak and an S1 width 210 thatfalls within the normal S1 width range. S2 _(G) is morphologicallycharacterized by a single peak and an S2 width 212 that falls within thenormal S2 width range.

“Regional” heart sound signals 202R and 202L are sensed simultaneouslyusing two sensors each primarily sensing heart sounds originated fromone portion of the heart, such as the right portion or the left portion.In one embodiment, heart sound signal 202R is sensed by a heart soundsensor placed within the RV, and heart sound signal 202L is sensed by aheart sound sensor placed within the LV. RV heart sound signal 202Rindicates S1 _(RV) (S1 sensed in the RV) and S2 _(RV) (S2 sensed in theRV). S1 _(RV) indicates tricuspid valve closure. S2 _(RV) indicatespulmonary valve closure. LV heart sound signal 202L indicates S1 _(LV)(S1 sensed in the LV) and S2 _(LV) (S2 sensed in the LV). S1 _(LV)indicates mitral valve closure. S2 _(LV) indicates aortic valve closure.

In a heart that contracts in synchrony, tricuspid valve closure (S1_(RV)) and mitral valve closure (S1 _(LV)) occur substantiallysimultaneously. The sounds of tricuspid valve closure and mitral valveclosure substantially overlap, producing the normal S1 _(G). Pulmonaryvalve closure (S2 _(RV)) and aortic valve closure (S2 _(RV)) occursubstantially simultaneously. The sounds of pulmonary valve closure andaortic valve closure substantially overlap, producing the normal S2_(G).

FIG. 3 is a graph illustrating heart sound signals indicative of cardiacmechanical dyssynchrony sensed by various heart sound sensors over acardiac cycle. A “global” heard sound signal 302G is sensed by a singleheart sound sensor sensing heart sounds originated from the entireheart. “Regional” heart sound signals 302R and 302L are sensedsimultaneously using two sensors each primarily sensing heart soundsoriginated from one portion of the heart. Heart sound signal 302Gcorresponds to heart sound signal 202G, heart sound signal 302Rcorresponds to heart sound signal 202R, and heart sound signal 302Lcorresponds to heart sound signal 202L. While signals 202G, 202R, and202L illustrates heart sound signals indicative cardiac synchrony,signals 302G, 302R, and 302L illustrates heart sound signals indicativecardiac dyssynchrony.

When the cardiac muscles in various regions of the heart fail tocontract in synchrony, i.e., when cardiac mechanical dyssynchronyoccurs, relative timing between the valve closures deviates from theirnormal timing. A delay 314 between tricuspid valve closure (S1 _(RV))and mitral valve closure (S1 _(LV)) indicates that the tricuspid valveand the mitral valve no longer close substantially simultaneously. Thedelay results in a double peaked S1 _(G), and/or an abnormally large S1width 310 associated with S1 _(G). A delay 316 between pulmonary valveclosure (S2 _(RV)) and aortic valve closure (S2 _(LV)) indicates thatthe pulmonary valve and the aortic valve no longer close substantiallysimultaneously. The delay results in a double peaked S2 _(G), and/or anabnormally large S2 width 312 associated with S2 _(G). Depends onindividual conditions, a heart that fails to contract in synchrony maybe indicated by one or more of delay 314 and delay 316 and/or one ormore of S1 width 310 and S2 width 312.

It is to be understood that the relative timing between S1 _(RV) and S1_(LV) and the relative timing between S2 _(RV) and S2 _(LV) as shown inFIG. 3 represents an example for illustrative purpose only. FIG. 3 showsexemplary heart sound signals of a patient suffering left bundle branchblock (LBBB), in which S1 _(RV) leads S1 _(LV) in time, and S2 _(RV)leads S2 _(LV) in time. However, the system and method discussed beloware generally applicable to cardiac mechanical dyssynchrony indicated byany one or more of delay 314, delay 316, an abnormally long S1 width310, and an abnormally long S2 width 312.

An effective treatment to resynchronize the heart shortens or eliminateseither or both delays 314 and 316 and restores both widths 310 and 312to their normal values. In other words, the goals of the treatmentinclude (i) merging the two peaks of SIG, and merging the two peaks ofS2 _(G), or (ii) realigning S1 _(RV) and S1 _(LV), and realigning S2_(RV) and S2 _(LV). In case the goal with respect to S1 and the goalwith respect to S2 cannot be both met, higher priority is given to thegoal of (i) merging the two peaks of S2 _(G), or (ii) realigning S2_(RV) and S2 _(LV).

One example of such treatment is the application of cardiacresynchronization therapy (CRT), which resynchronizes the contractionsof the heart, particularly the ventricles, by delivering ventricularpacing pulses using proper timing. The extent to which a therapyrestores cardiac synchrony is indicated by the extent to which delay 314or 316 are reduced, or by the extent to which width 310 and 312 returnedto their normal values.

In system and method descriptions below, heart sound signals 302G, 302R,and 302L, and heart sounds S1 _(G), S2 _(G), S1 _(RV), S2 _(RV), S1_(LV), and S2 _(RV) are used for illustrative, but not restrictive,purposes. Heart sound signal 302G generally includes a “global” heartsound sensed by a single sensor and indicative of heart soundsoriginating from anywhere in the heart. Heart sound signals 302R and302L include two heart sound signals simultaneously by two sensors.Heart sound signal 302R generally includes a “regional” heart soundindicative of primarily heart sounds originating from the right side ofthe heart, sensed by such as a sensor placed in the RV. Heart soundsignal 302L generally includes another “regional” heart sound indicativeof primarily heart sounds originating from the left side of the heart,sensed by such as a sensor placed in the LV. S1 _(G) generally includesa heart sound resulted from a combination of tricuspid valve closure andmitral valve closure. S2 _(G) generally includes a heart sound resultedfrom a combination of pulmonary valve closure and aortic valve closure.S1 _(RV) generally includes a heart sound resulted from tricuspid valveclosure. S2 _(RV) generally includes a heart sound resulted frompulmonary valve closure. S1 _(LV) generally includes a heart soundresulted from mitral valve closure. S2 _(LV) generally includes a heartsound resulted from aortic valve closure. S1 generally refers to theheart sound type known as the “first heart sound,” or as one or moreoccurrences of the “first heart sounds,” including S1 _(G), S1 _(RV),and S1 _(LV). S2 generally refers to a heart sound type known as the“second heart sound,” or as one or more occurrences of the “second heartsounds,” including S2 _(G), S2 _(RV), and S2 _(RV).

FIG. 4 is a block diagram illustrating one embodiment of a system 400for optimizing pacing parameters based on a cardiac mechanicaldyssynchrony assessment. System 400 includes a heart sound sensor 402, aheart sound signal processor 403, a respiratory sensor 404, arespiratory signal processor 405, a cardiac mechanical dyssynchronyassessment module 410, a pacing parameter optimization module 430, apacing controller 432, and a pacing circuit 434. In one embodiment,portions of system 400 are implemented as a computer-based system.

Heart sound sensor 402 includes one or more sensors each sense a signalindicative of heart sounds. Examples of the one or more sensors includeaccelerometers and microphones. In one embodiment, heart sound sensor402 includes a single heart sound sensor to sense a heart sound signal302G. In one specific embodiment, the single heart sound sensor isplaced external to the heart. In another specific embodiment, the singleheart sound sensor is placed within a heart chamber. In anotherembodiment, heart sound sensor 402 is a sensor system including aplurality of heart sound sensors each sensing a signal indicative ofheart sounds originating from a particular portion of the heart. In onespecific embodiment, the plurality of heart sound sensors include an RVheart sound sensor to sense heart sound signal 302R and an LV heartsound sensor to sense heart sound signal 302L. In one specificembodiment, the RV heart sound sensor is an intracardiac heart soundsensor for placement in the RV to sense a heart sound signal indicativeof at least tricuspid valve closure and pulmonary valve closure, and theLV heart sound sensor is another intracardiac heart sound sensor forplacement in the LV to sense a heart sound signal indicative of at leastmitral valve closure and aortic valve closure. In another specificembodiment, the RV heart sound sensor is the intracardiac heart soundsensor for placement in the RV to sense the heart sound signalindicative of at least tricuspid valve closure and pulmonary valveclosure, and the LV heart sound sensor is an epicardial heart soundsensor for placement on the epicardial wall over the LV to sense a heartsound signal indicative of at least mitral valve closure and aorticvalve closure.

Heart sound signal processor 403 conditions the one or more heart soundsignals sensed by heart sound sensor 402. Heart sound signal processor403 includes an envelope detector to produce heart sound signal 302Gand/or heart sound signals 302R and 302L. In one embodiment, heart soundsignal processor 403 further includes an ensemble averaging circuit toimprove a signal-to-noise ratio of each of the one or more heart soundsignals by ensemble averaging.

Respiratory sensor 404 senses a respiratory signal indicative ofrespiratory cycles each including an inspiratory phase and expiratoryphase. In one embodiment, respiratory sensor 404 includes anaccelerometer sensing an acceleration signal indicative of inspirationand expiration. In another embodiment, respiratory sensor 404 includes aminute ventilation sensor. In one specific embodiment, the minuteventilation sensor is an implantable impedance sensor sensing a thoracicimpedance indicative of minute ventilation.

Respiration signal processor 405 conditions the respiratory signal foruse by cardiac mechanical dyssynchrony assessment module 410. In oneembodiment, respiration signal processor 405 includes an expirationdetector to detect and indicate each expiratory phase of the respiratorycycle.

Cardiac mechanical dyssynchrony assessment module 410 produces one ormore dyssynchrony parameters each indicative of a degree of cardiacmechanical dyssynchrony based on at least the one or more heart soundsignals sensed by heart sound sensor 402 and preprocessed by heart soundsignal processor 403. Cardiac mechanical dyssynchrony assessment module410 includes a heart sound input 412, a respiratory signal input 413, aheart sound detector 414, and a heart sound morphology analyzer 420. Inone embodiment, cardiac mechanical dyssynchrony assessment module 410 isimplemented as a computer-based system. In one specific embodiment,cardiac mechanical dyssynchrony assessment module 410 produces the oneor more dyssynchrony parameters by executing an automated cardiacmechanical dyssynchrony algorithm using at least the one or more heardsound signals and/or detected S1 and S2 as input.

Heart sound input 412 receives the one or more heart sound signals, suchas heart sound signal 302G and/or heart sound signals 302R and 302L.Respiratory signal input 413 receive the respiratory signal indicativeof which occurrences of S2 _(G) and/or S2 _(RV) and S2 _(LV) aredetected during an expiratory phase.

Heart sound detector 414 detects heart sounds from the one or more heartsound signals. Heart sound detector 414 includes at least an S1 detector416 and an S2 detector 418. In one embodiment, S1 detector 416 detectsSIG, and S2 detector 418 detects S2 _(G), both from heart sound signal302G. In another embodiment, S1 detector 416 detects S1 _(RV) from heartsound signal 302R and S1 _(LV) from heart sound signal 302L, and S2detector 418 detects S2 _(RV) from heart sound signal 302R and S2 _(LV)from heart sound signal 302L.

Heart sound morphology analyzer 420 produces one or more dyssynchronyparameters. In one embodiment, heart sound morphology analyzer 420 is acomputer-based analyzer that produces the one or more dyssynchronyparameters by executing the automated cardiac mechanical dyssynchronyalgorithm. The automated cardiac mechanical dyssynchrony algorithm isdesigned to detect morphological features of detected S1 and S2, makemeasurements related to the morphological features, and produce the oneor more dyssynchrony parameters based on results of the measurements, asdescribed below.

Heart sound morphology analyzer 420 includes at least an S1 morphologyanalyzer 422 to produce a dyssynchrony parameter related to S1 _(G) (orS1 _(RV) and S1 _(LV)) and an S2 morphology analyzer 426 to produceanother dyssynchrony parameter related to S2 _(G) (or S2 _(RV) and S2_(LV)). In one embodiment, S2 morphology analyzer 426 to produce thedyssynchrony parameter related to S2 _(G) (or S2 _(RV) and S2 _(LV))based on only on S2 _(G) (or S2 _(RV) and S2 _(LV)) detected during anexpiratory phase of the respiratory cycle. Heart sound morphologyanalyzer 420 includes one or more heart sound measurement modules tomeasure parameters associated with the morphological features of the oneor more heart sounds. S1 morphology analyzer 422 includes an S1measurement module 424. S2 morphology analyzer 426 includes an S2 widthmeasurement module 428.

In one embodiment, each heart sound measurement module includes a heartsound width measurement module to measure widths of the heart sounds. S1measurement module 424 includes an S1 width measurement module tomeasure S1 width 310 (the width of S1 _(G)). S2 measurement module 428includes an S2 width measurement module to measure S2 width 312 (thewidth of S2 _(G)).

In another embodiment, each heart sound measurement module includes aheart sound delay measurement modules to measure delays in cardiac valveclosure as indicated by heart sounds in a single heart sound signal suchas heart sound signal 302G. Each heart sound delay measurement moduleincludes a peak detector and a timer. The peak detector detects peakswithin a heart sound each indicating one valve closure. If two peaks aredetected within the heart sound, the timer measures the delay as thetime interval between the two peaks. In this embodiment, S1 measurementmodule 424 includes an S1 delay measurement measure to measure S1 delay314 as a time interval between two peaks detected within S1 _(G). S2measurement module 428 includes an S2 delay measurement measure tomeasure S2 delay 316 as a time interval between two peaks detectedwithin S2 _(G). In one embodiment, an imaging technique, such as tissueDoppler imaging (TDI), echocardiography, or magnetic resonance imaging(MRI), is applied to differentiate between the two peaks of SIG. Thisprovides for identification of the peak associated with tricuspid valveclosure and the peak associated with mitral valve closure in S1 _(G).Normally, the pulmonary valve closure is delayed during an inspiratoryphase. In one embodiment, this fact is utilized to differentiate betweenthe two peaks of S2 _(G). This provides for identification of the peakassociated with pulmonary valve closure and the peak associated withaortic valve closure in S2 _(G). In one embodiment, each heart soundmeasurement modules of morphology analyzer 420 is calibrated on aperiodic basis or as needed using these peak identification techniques.

In another embodiment, each heart sound measurement module includes aheart sound delay measurement modules to measure delays in cardiac valveclosure as indicated by heart sounds in two heart sound signals such asheart sound signals 302R and 302L. Each heart sound delay measurementmodule includes a timer to measure the delay being a time intervalbetween a heart sound detected in one heart sound signal and the heartsound detected in another heart sound signal. In this embodiment, S1measurement module 424 includes an S1 delay measurement module tomeasure S1 delay 314 as the time interval between S1 _(RV) and S1 _(LV).S2 measurement module 428 includes an S2 delay measurement module tomeasure S2 delay 316 as the time interval between S2 _(RV) and S2 _(LV).

In another embodiment, heart sound morphology analyzer 420 includes aheart sound time-frequency analyzer to produce at least onetime-frequency representation for each of the one or more heart soundsignals and produce the one or more dyssynchrony parameters eachassociated with at least one feature of the one time-frequencyrepresentation. In one embodiment, the heart sound time-frequencyanalyzer further produces a parameter indicative of pulmonary arterypressure based on at least one feature of the time-frequencyrepresentation. The heart sound time-frequency analyzer includes, by wayof example, and not by way of limitation, one or more of a short-timeFourier transform (STFT) module, a reduced interference (RID) module,and a wavelet transform (WT) module. The STFT module produces a timeversus frequency representation of the signal by applying a slidingwindow to data representing the one or more heart sound signals. Aspectral representation based on a windowed Fourier transform (FT) iscomputed each time the window position is updated. The RID moduleprovides an improvement in resolution over the STFT based on theWigner-Ville time-frequency distribution by presenting a result withreduced interference. The WT module takes advantage of the fact thathigher frequencies are better resolved in time while lower frequenciesare better resolved in frequency. This processing involves recursivelyfiltering the data representing the one or more heart sound signals atdifferent scales with sets of high-pass and low-pass filters.

Pacing parameter optimization module 430 determines one or moreapproximately optimal pacing parameters based on the one or moredyssynchrony parameters. The approximately optimal pacing parametersprovide for an approximately minimum degree of cardiac mechanicaldyssynchrony. Pacing controller 432 controls the delivery of pacingpulses to the heart from pacing circuit 434 using parameters provided bypacing parameter optimization module 430 for evaluating the parametersby their effects on the degree of cardiac mechanical dyssynchrony. Theapproximately optimal pacing parameters are determined by selectingparameters associated with the lowest degree of degree of cardiacmechanical dyssynchrony, as indicated by the one or more dyssynchronyparameters, from all the parameters evaluated.

In one embodiment, pacing parameter optimization module 430 optimizesone or more pacing parameters by adjusting the one or more pacingparameters for an approximately optimal value of each of the one or moredyssynchrony parameters. The approximately optimal value is a valueassociated with the minimum degree of cardiac mechanical dyssynchronyobtained by the adjusting the one or more pacing parameters. Pacingparameter optimization module 430 includes a parameter adjustmentcircuit to adjust the one or more pacing parameters. The parameteradjustment circuit includes, but is not limited to, one or more of apacing site selector, an atrioventricular delay (AVD) adjustmentcircuit, and an interventricular delay (IVD) adjustment circuit. Thepacing site selector selects one or more pacing sites to which thepacing pulses are delivered. The AVD adjustment circuit adjusts one ormore AVDs at which ventricular pacing pulses are delivered. The IVDadjustment circuit adjusts one or more IVDs at which ventricular pacingpulses are delivered. After each adjustment of any one or more of thepacing sites, AVDs, and IVDs, pacing controller 432 controls thedelivery of the pacing pulses from pacing circuit 434 using the adjustedparameters. The optimization process includes repeated parameteradjustments and deliveries of pacing pulses using the adjustedparameters until an approximately minimum or otherwise satisfactorydegree of cardiac mechanical dyssynchrony is reached.

In another embodiment, pacing parameter optimization module 430optimizes one or more pacing parameters by testing various combinationsof values for the one or more pacing parameters for their effects on thedegree of cardiac mechanical dyssynchrony. Pacing parameter optimizationmodule 430 includes a parameter generator to generate a plurality ofpacing parameter value sets each including a value for each of the oneor more pacing parameters. The parameter generator includes, but is notlimited to, one or more of a pacing site generator, an AVD generator,and an IVD generator. The pacing site generator generates a plurality ofpacing sites or pacing site combinations to which the pacing pulses aredelivered. The AVD generator generates a plurality of AVDs at whichventricular pacing pulses are delivered. The IVD generator generates aplurality of IVDs at which ventricular pacing pulses are delivered. Inone embodiment where more than one pacing parameter is being tested,each of the pacing parameter value sets includes a unique combination ofvalues for the tested parameters. Pacing controller 432 controls thedelivery of a plurality of pacing pulse sequences from pacing circuit434. Each sequence includes a plurality of pacing pulses delivered usingone of the pacing parameter value sets. The optimization processincludes identifying the pacing parameter value set that produces anapproximately minimum or otherwise satisfactory degree of cardiacmechanical dyssynchrony. In one embodiment, pacing parameteroptimization module 430 includes an optimal parameter selector to selectan optimal parameter value set associated with the minimum degree ofcardiac mechanical dyssynchrony produced by pacing during theoptimization process.

It is to be understood that while optimization of pacing parameters, andparticularly the pacing sites, AVDs, and IVDs are discussed as examples,the idea of adjusting or optimizing a therapy using a measure of cardiacmechanical dyssynchrony is not limited to the optimization of pacingtherapy. The basic concept of adjusting or optimizing a therapy bydetermining therapy parameters providing for a minimum degree of cardiacmechanical dyssynchrony generally applies to the optimization of otherpacing parameters and other therapies including, but not being limitedto, other electrical therapies, physical therapies, chemical therapies,and biological therapies.

FIG. 5 is an illustration of one embodiment of a cardiac rhythmmanagement (CRM) system 500 and portions of the environment in whichsystem 500 is used. System 500 includes an implantable system 505, anexternal system 555, and a telemetry link 540 providing forcommunication between implantable system 505 and external system 555.

Implantable system 505 includes, among other things, implantable medicaldevice 510 and lead system 508. In various embodiments, implantablemedical device 510 is an implantable CRM device including one or more ofa pacemaker, a cardioverter/defibrillator, a cardiac resynchronizationtherapy (CRT) device, a cardiac remodeling control therapy (RCT) device,a drug delivery device, and a biological therapy device. In oneembodiment, implantable medical device 510 includes implantable sensorsfor sensing the signals used by cardiac mechanical dyssynchronyassessment module 410 and pacing parameter optimization module 430. Inanother embodiment, implantable medical device 510 and lead system 508each include one or more of the implantable sensors. As shown in FIG. 5,implantable medical device 510 is implanted in a body 502. Lead system508 provides connections between implantable medical device 510 and aheart 501. In various embodiments, lead system 508 includes leads forsensing physiological signals and delivering pacing pulses,cardioversion/defibrillation shocks, and/or pharmaceutical or othersubstances. In one embodiment, at least one implantable sensor isincorporated into a lead of lead system 508 for placement in or aboutheart 501.

In one embodiment, external system 555 is a patient management systemincluding external device 550, network 560, and remote device 570.External device 550 is within the vicinity of implantable medical device510 and communicates with implantable medical device 510bi-directionally via telemetry link 540. Remote device 570 is in aremote location and communicates with external device 550bi-directionally via network 560, thus allowing a user to monitor andtreat a patient from a distant location. In another embodiment, externalsystem includes a programmer communicating with implantable medicaldevice 510 bi-directionally via telemetry link 540.

System 500 includes system 400 for optimizing pacing parameters based onthe cardiac mechanical dyssynchrony assessment. In one embodiment,system 500 also serves diagnostic and/or other therapeutic purposes byproviding the user with heart sound signals indicative of cardiacmechanical dyssynchrony and/or other cardiovascular conditions. Thedistribution of system 400 in system 500 depends on design and patientmanagement considerations, such as the size and power consumption ofeach system component and the ability of monitoring the patient invarious settings from various locations. In one embodiment, implantablemedical device 510 includes the entire system 400. In anotherembodiment, implantable medical device 510 includes portions of system400, and external system 555 includes the remaining portions of system400. One specific embodiment is discussed below with reference to FIG. 6as an example, but not a limitation.

FIG. 6 is a block diagram illustrating one embodiment of a circuit ofsystem 500, including implantable system 505, external system 555, andtelemetry link 540 wirelessly coupling the two systems.

Implantable system 505 includes lead system 508, heart sound sensor 402,respiratory sensor 404, and implantable medical device 510. Lead system508 includes pacing leads each having at least one electrode to beplaced in a heart chamber. Each pacing lead allows delivery of pacingpulses to, and sensing of cardiac electrical activity from, a cardiaclocation where the electrode is placed. In one embodiment, lead system508 includes one or more atrial pacing leads and one or more ventricularpacing leads. The one or more atrial pacing leads include at least oneRA pacing lead. The one or more ventricular pacing leads include one ormore RV pacing lead and/or one or more LV pacing leads. In oneembodiment, heart sound sensor 402 includes one sensor housed inimplantable medical device 510 to sense heart sound signal 302G. Inanother embodiment, heart sound sensor 402 includes one intracardiacsensor incorporated into a pacing lead of lead system 508 for placementwithin a heart chamber to sense heart sound signal 302G. In anotherembodiment, heart sound sensor 402 includes one intracardiac sensorincorporated into an RV pacing lead to sense heart sound signal 302R andanother intracardiac sensor or epicardial sensor incorporated into an LVpacing lead to sense heart sound signal 302L. In one embodiment,respiratory sensor 404 is housed in implantable medical device 510. Inanother embodiment, respiratory sensor 404 is incorporated into a pacinglead of lead system 508 for placement within a heart chamber.Implantable medical device 510 includes pacing circuit 434, a sensingcircuit 603, an implant controller 636, and an implant telemetry module642. Pacing circuit 434 produces pacing pulses and delivers the pacingpulses to the heart through lead system 508. Sensing circuit 603 senseselectrograms indicative of cardiac electrical activities. Implantcontroller 636 includes at least pacing controller 432, heart soundsignal processor 403, and respiratory signal processor 405. Pacingcontroller 432 controls pacing circuit 434 by executing a selectedpacing algorithm using at least the cardiac activities sensed by sensingcircuit 603 and pacing parameters programmed into implant controller 636as inputs.

External system 555 includes an external telemetry module 644 and anexternal controller 652. External controller 652 includes cardiacmechanical dyssynchrony assessment module 410 and pacing parameteroptimization module 430. In one embodiment, in which external system 555includes external device 550, network 560, and remote device 570, remotedevice 570 includes cardiac mechanical dyssynchrony assessment module410 and pacing parameter optimization module 430. This allows long-termtherapy optimization performed by the user, or by system 500automatically, in a location away from the patient's presence. In oneembodiment, system 500 provides for therapy optimization on a continuousbasis. In another embodiment, system 500 provides for therapyoptimization on a predetermined schedule, such as on a periodic basis.In another embodiment, system 500 provides for therapy optimization inresponse to a change of patient condition detected by or throughimplantable system 505. In another embodiment, system 500 provides fortherapy optimization in response to a command entered by the user. Thetherapy optimization results in one or more optimal pacing parametervalues to be programmed into implant controller 636.

Implant telemetry module 642 and external telemetry module 644 supporttelemetry link 540. Telemetry link 540 is a wireless bidirectional datatransmission link. In one embodiment, telemetry link 540 is an inductivecouple formed when two coils—one connected to implant telemetry module642 and the other connected to external telemetry module 644—are placednear each other. In this embodiment, the patient or the user places thecoil connected to external device 550 on body 502 over implantablemedical device 510. In another embodiment, telemetry link 540 is afar-field radio-frequency telemetry link allowing implantable medicaldevice 510 and external device 550 to communicate over a telemetry rangethat is at least ten feet. In one embodiment, implant telemetry module642 transmits the heart sound and respiratory signals acquired byimplantable system 505, and external telemetry module 644 receives thesesignals.

FIG. 7 is a flow chart illustrating one embodiment of a method foroptimizing pacing parameters based on the cardiac mechanicaldyssynchrony assessment. In one embodiment, the method is performed bysystem 400.

One or more heart sound signals indicative of at least S1 and S2 aresensed at 700. In one embodiment, the one or more heart sound signalsinclude one or more acceleration signals indicative of the heart'smechanical vibrations. In another embodiment, the one or more heartsound signals include one or more audio signals originated from theheart. In one embodiment, heart sound signal 302G is sensed at 700. Inanother embodiment, heart sound signals 302R and 302L are sensed at 700.In another embodiment, both heart sound signal 302G and heart soundsignals 302R and 302L are sensed at 700. In one embodiment, arespiratory signal indicative of respiratory cycles each including aninspiratory phase and expiratory phase is also sensed. In one specificembodiment, the respiratory signal includes an impedance signalindicative minute ventilation.

The one or more heart sound signals are processed at 710. The processincludes envelope-detecting the one or more heart sound signals byrectification and low-pass filtering. In one embodiment, eachenvelope-detected heart sound signal is ensemble averaged to improve itssignal-to-noise ratio. In one embodiment, the respiratory signal is alsoprocessed at 710. The process includes detection of expiratory phases.

Cardiac mechanical dyssynchrony is assessed based on the one or moreheart sound signals at 720. The one or more heart sound signals arereceived at 722. In one embodiment, the respiratory signal is alsoreceived at 722. In one embodiment, only S2 _(G), and/or S2 _(RV) and S2_(LV), that occur during the expiratory phase of the respiratory cycleare used for the assessment of cardiac mechanical dyssynchrony. S1 andS2 are detected from the one or more heart sound signals at 724. In oneembodiment, S1 _(G) and S2 _(G) are detected from heart sound signal302G. In another embodiment, S1 _(RV) and S2 _(RV) are detected fromheart sound signal 302R, and S1 _(LV) and S2 _(LV) are detected fromheart sound signal 302L. One or more dyssynchrony parameters eachindicative of the degree of cardiac mechanical dyssynchrony are producedbased on morphological features of, or related to, S1 and S2 at 726. Inone embodiment, an automated cardiac mechanical dyssynchrony algorithmis executed to detect morphological features of detected S1 and S2, makemeasurements related to the morphological features, and produce the oneor more dyssynchrony parameters based on results of the measurements at726. The morphological features indicate cardiac valve closure delays.In one embodiment, a first dyssynchrony parameter related to S1 and asecond dyssynchrony parameter related to S2 are produced at 726. Theproduction of the dyssynchrony parameters includes measuring one or moreparameters associated with the morphological features.

In one embodiment, S1 width 310 and S2 width 312 are measured from heartsound signal 302G. In another embodiment, S1 delay 314 and S2 delay 316are measured from heart sound signal 302G. S1 delay 314 is measured asthe time interval between the peak of S1 _(G) associated with mitralvalve closure and the peak of S1 _(G) associated with tricuspid valveclosure. S2 delay 316 is measured as the time interval between the peakS2 _(G) associated with aortic valve closure and the peak S2 _(G)associated with pulmonary valve closure. In another embodiment, S1 delay314 and S2 delay 316 are measured from heart sound signals 302R and302L. S1 delay 314 is measured as the time interval between S1 _(RV) andS1 _(LV). S2 delay 316 is measured as the time interval between S2 _(RV)and S2 _(LV). In another embodiment, at least one time-frequencyrepresentation for each of the one or more heart sound signals isproduced. The time-frequency representation is produced by, for example,performing one or more of STFT, RID, and WT. One or more dyssynchronyparameters are produced each based on at least one feature in thetime-frequency representation. In a further embodiment, a parameter isproduced to indicate pulmonary artery pressure based on at least onefeature in the time-frequency representation.

One or more pacing parameters are optimized at 730, based on the one ormore dyssynchrony parameters produced at 726. The one or more parametersare optimized when the one or more dyssynchrony parameters indicate anapproximately minimum degree of cardiac mechanical dyssynchrony. In oneembodiment, the one or more pacing parameters are optimized based on atleast one dyssynchrony parameter produced based on S2 measurements. Theoptimization is to minimize the time interval between pulmonary valveclosure and aortic valve closure. In another embodiment, the one or morepacing parameters are optimized based on at least one dyssynchronyparameter produced based on S1 measurements. The optimization is tominimize the time interval between tricuspid valve closure and mitralvalve closure. In another embodiment, the one or more pacing parametersare optimized based on dyssynchrony parameters produced based on both S1and S2 measurements. If the time interval between pulmonary valveclosure and aortic valve closure and the time interval between tricuspidvalve closure and mitral valve closure cannot be minimized with the sameone or more pacing parameters, the minimization of the time intervalbetween pulmonary valve closure and aortic valve closure has a higherpriority.

In one embodiment, the one or more pacing parameters are adjusted for anapproximately optimal value of each of the one or more dyssynchronyparameters. The approximately optimal value is a value associated withan approximately minimum degree of cardiac mechanical dyssynchronyobtained by adjusting the one or more pacing parameters. Adjusting theone or more pacing parameters includes, but is not limited to, selectingone or more pacing sites to which the pacing pulses are delivered,adjusting one or more AVDs at which ventricular pacing pulses aredelivered, and adjusting one or more IVDs at which ventricular pacingpulses are delivered. After each parameter adjustment, a plurality ofpacing pulses is delivered to the heart using the one or more adjustedpacing parameters. The optimization process includes repeated parameteradjustments and delivery of pacing pulses using the adjusted parametersuntil an approximately minimum or otherwise satisfactory degree ofcardiac mechanical dyssynchrony is reached.

In another embodiment, the one or more pacing parameters are optimizedby testing the effects of various combinations of values of the one ormore pacing parameters on the one or more dyssynchrony parameters. Aplurality of pacing parameter value sets is generated. Each pacingparameter value set includes a value for each of the one or more pacingparameters. Generating the plurality of pacing parameter value setsincludes, but is not limited to, generating a plurality of pacing sitesor pacing site combinations to which pacing pulses are delivered,generating a plurality of AVDs at which ventricular pacing pulses aredelivered, and generating a plurality of IVDs at which ventricularpacing pulses are delivered. After the plurality of pacing parametervalue sets are delivered, a plurality of pacing pulse sequences aredelivered. Each sequence includes a plurality of pacing pulses deliveredusing one pacing parameter value set of the plurality of pacingparameter value sets. An optimal parameter value set is selected fromthe plurality of pacing parameter value sets. The optimal pacingparameter value set is associated with an approximately optimal value ofat least one of the one or more dyssynchrony parameters. Theapproximately optimal value is associated with a minimum degree ofcardiac mechanical dyssynchrony obtained by pacing with the plurality ofpacing parameter sets.

It is to be understood that the above detailed description is intendedto be illustrative, and not restrictive. For example, the method forassessing the cardiac mechanical dyssynchrony can be performed by anon-implantable system. The method for optimizing pacing parameters canapply to optimization of parameters of therapies other than cardiacpacing. Other embodiments, including any possible permutation of thesystem components discussed in this document, will be apparent to thoseof skill in the art upon reading and understanding the abovedescription. The scope of the invention should, therefore, be determinedwith reference to the appended claims, along with the full scope ofequivalents to which such claims are entitled.

1. A system for analyzing a heart having a first cardiac valve and asecond cardiac valve, the system comprising: a heart sound input toreceive one or more signals each indicative of heart sounds; a heartsound detector, coupled to the heart sound input, to detect heart soundsof at least one predetermined type from the one or more signals; and acomputer-based heart sound morphology analyzer, coupled to the heartsound detector, to produce at least one dyssynchrony parameterindicative of a degree of cardiac mechanical dyssynchrony, the heartsound morphology analyzer including a heart sound measurement module tomeasure one or more parameters each based on at least one morphologicalfeature of the heart sounds of the at least one predetermined type, theat least one morphological feature indicative of a time interval betweenclosures of the first cardiac valve and the second cardiac valve in onecardiac cycle.
 2. The system of claim 1, wherein the heart sounds of theat least one predetermined type comprise the first heart sounds (S1),and wherein the heart sound morphology analyzer comprises an S1morphology analyzer to produce a first dyssynchrony parameter related toS1, the S1 morphology analyzer including an S1 measurement module tomeasure one or more parameters each based on at least an S1morphological feature indicative a first time interval between atricuspid valve closure and a mitral valve closure.
 3. The system ofclaim 1, wherein the heart sounds of the at least one predetermined typecomprise the second heart sounds (S2), and wherein the heart soundmorphology analyzer comprises an S2 morphology analyzer to produce asecond dyssynchrony parameter related to S2, the S2 morphology analyzerincluding an S2 measurement module to measure one or more parameterseach based on at least an S2 morphological feature indicative of asecond time interval between a pulmonary valve closure and an aorticvalve closure.
 4. The system of claim 1, wherein the heart sound inputreceives one or more signals indicative of first heart sounds (S1) andsecond heart sounds (S2), the heart sound detector detects S1 and S2,and the heart sound morphology analyzer comprises: an S1 morphologyanalyzer to produce a first dyssynchrony parameter related to S1, the S1morphology analyzer including an S1 measurement module to measure one ormore parameters each based on at least an S1 morphological featureindicative a first measured time interval between a tricuspid valveclosure and a mitral valve closure; and an S2 morphology analyzer toproduce a second dyssynchrony parameter related to S2, the S2 morphologyanalyzer including an S2 measurement module to measure one or moreparameters each based on at least an S2 morphological feature indicativeof a second measured time interval between a pulmonary valve closure andan aortic valve closure.
 5. The system of claim 4, wherein the heartsound input comprise: a right-ventricular heart sound input to receive asignal indicative of at least S1 sensed from a right ventricle (S1_(RV)) and S2 sensed from the right ventricle (S2 _(RV)); and aleft-ventricular heart sound input to receive a signal indicative of atleast S1 sensed from a left ventricle (S1 _(LV)) and S2 sensed from theleft ventricle (S2 _(LV)), and wherein: the S1 heart sound measurementmodule comprises an S1 delay measurement module to measure an S1 delaybeing a time interval between S1 _(RV) and S1 _(LV); and the S2 heartsound measurement module comprises an S2 delay measurement module tomeasure an S2 delay being a time interval between S2 _(RV) and S2 _(LV).6. The system of claim 5, further comprising a first implantable heartsensor adapted to sense the signal indicative of at least S1 _(RV) andS2 _(RV) and a second implantable heart sensor adapted to sense thesignal indicative of at least S1 _(LV) and S2 _(LV).
 7. The system ofclaim 4, wherein: the S1 heart sound measurement module comprises an S1width measurement module to measure an S1 width; and the S2 heart soundmeasurement module comprises an S2 width measurement module to measurean S2 width.
 8. The system of claim 4, wherein the S1 heart soundmeasurement module comprises an S1 delay measurement module to measurean S1 delay being a time interval between a morphological featureindicative of the tricuspid valve closure and a morphological featureindicative of the mitral valve closure; and the S2 heart soundmeasurement module comprises an S2 delay measurement module to measurean S2 delay being a time interval between a morphological featureindicative of the pulmonary valve closure and a morphological featureindicative of the aortic valve closure.
 9. The system of claim 4,further comprising at least one implantable heart sound sensor to sensea signal indicative of at least S1 and S2.
 10. The system of claim 9,further comprising an ensemble averaging circuit to ensemble average thesignal indicative of at least S1 and S2.
 11. The system of claim 4,further comprising a respiratory signal input to receive a respiratorysignal indicative of an inspiratory phase and an expiratory phase of arespiratory cycle, and wherein at least the S2 heart sound measurementmodule is adapted to measure the one or more parameters during theexpiratory phase.
 12. The system of claim 11, further comprising animplantable respiratory sensor to sense the respiratory signal.
 13. Thesystem of claim 12, wherein the implantable respiratory sensor comprisesan implantable accelerometer to sense an acceleration signal indicativeof inspiration and expiration.
 14. The system of claim 12, wherein theimplantable respiratory sensor comprises an implantable impedance sensorto sense an impedance signal indicative of minute ventilation.
 15. Thesystem of claim 1, wherein the heart sound morphology analyzer comprisesa heart sound time-frequency analyzer to produce at least onetime-frequency representation for each of the one or more signals andproduce the at least one dyssynchrony parameter based on the at leastone time-frequency representation.
 16. The system of claim 15, whereinthe heart sound time-frequency analyzer is adapted to further produce aparameter indicative of pulmonary artery pressure based on at least onefeature in the at least one time-frequency representation.
 17. Thesystem of claim 15, wherein the heart sound time-frequency analyzercomprises a short-time Fourier transform (STET) module.
 18. The systemof claim 15, wherein the heart sound time-frequency analyzer comprises areduced interference (RID) module.
 19. The system of claim 15, whereinthe heart sound time-frequency analyzer comprises a wavelet transform(WT) module.
 20. The system of claim 1, further comprising a pacingparameter optimization module adapted to optimize one or more pacingparameters based on the at least one dyssynchrony parameter.
 21. Thesystem of claim 20, wherein the parameter optimization module is adaptedto optimize one or more pacing parameters by adjusting the one or morepacing parameters for an approximately optimal value for the at leastone dyssynchrony parameter, and wherein the pacing parameteroptimization module comprises a parameter adjustment circuit to adjustthe one or more pacing parameters.
 22. The system of claim 21, whereinthe parameter adjustment circuit comprises a pacing site selector toselect one or more pacing sites to which pacing pulses are delivered.23. The system of claim 21, wherein the parameter adjustment circuitcomprises an atrioventricular delay (AVD) adjustment circuit to adjustone or more AVDs at which ventricular pacing pulses are delivered. 24.The system of claim 21, wherein the parameter adjustment circuitcomprises an interventricular delay (IVD) adjustment circuit to adjustone or more IVDs at which ventricular pacing pulses are delivered. 25.The system of claim 20, further comprising: a pacing circuit to deliverpacing pulses; and a pacing controller, coupled to the pacing circuitand the pacing parameter optimization module, wherein the pacingparameter optimization module comprises a pacing parameter generator togenerate a plurality of pacing parameter sets each including one or moreadjustable pacing parameters, and wherein the pacing controller isadapted to control a delivery of a plurality of the pacing pulsesequences each including a plurality of pacing pulses delivered usingone pacing parameter set of the plurality of pacing parameter sets. 26.The system of claim 25, wherein the pacing parameter optimization modulecomprises an efficacy analyzer to relate each pacing parameter set ofthe plurality of pacing parameter sets to a value of the at least onedyssynchrony parameter.
 27. The system of claim 26, wherein the pacingparameter optimization module further comprises an optimal parameterselector to select an optimal parameter set of the plurality ofparameter sets, the optimal parameter set associated with a minimumvalue of the at least one dyssynchrony parameter.
 28. The system ofclaim 25, wherein the pacing parameter generator comprises a pacing sitegenerator to generate a plurality of pacing sites to one or more ofwhich the pacing pulses are delivered.
 29. The system of claim 25,wherein the pacing parameter generator comprises an atrioventriculardelay (AVD) generator to generate a plurality of AVDs at whichventricular pacing pulses are delivered.
 30. The system of claim 25,wherein the pacing parameter generator comprises an interventriculardelay (IVD) generator to generate a plurality of IVDs at whichventricular pacing pulses are delivered.
 31. A system for analyzing aheart having a first cardiac valve and a second cardiac valve, thesystem comprising: an implantable system including: one or moreimplantable heart sound sensors to sense one or more heart sound signalseach indicative of heart sounds of at least one predetermined type; andan implantable medical device including: an implant controller, coupledto the one or more implantable heart sound sensors, to process the oneor more heart sound signals; and an implant telemetry module, coupled tothe implantable controller, to transmit the one or more heart soundsignals; an external system communicatively coupled to the implantablemedical device, the external system including: an external telemetrymodule to receive the one or more heart sound signals; and an externalcontroller coupled to the external telemetry module, the externalcontroller including a heart sound morphology analyzer to produce atleast one dyssynchrony parameter indicative of a degree of cardiacmechanical dyssynchrony, the heart sound morphology analyzer including aheart sound measurement module to measure one or more parameters eachbased on at least one morphological feature of the heart sounds of theat least one predetermined type, the at least one morphological featureindicative of a time interval between closures of the first cardiacvalve and the second cardiac valve in one cardiac cycle.
 32. The systemof claim 31, wherein the implantable medical device comprises ahermetically sealed housing, and wherein at least one of the one or moreheart sound sensors are housed within the hermetically sealed housing.33. The system of claim 31, wherein the implantable medical devicecomprises a pacing circuit, and the implantable system further comprisesone or more pacing leads coupled to the pacing circuit, wherein at leastone of the one or more heart sound sensors is incorporated into the oneof the one or more pacing leads.
 34. The system of claim 33, wherein theone or more pacing leads comprise a right ventricular (RV) pacing leadincluding at least an RV electrode and a left ventricular (LV) pacinglead include at least an LV electrode, wherein the one or more heartsound sensors comprise an RV heart sound sensor incorporated into the RVpacing lead near the RV electrode and an LV heart sound sensorincorporated into the LV pacing lead near the LV electrode.
 35. Thesystem of claim 31, wherein the one or more heart sound sensors compriseat least one accelerometer.
 36. The system of claim 31, wherein the oneor more heart sound sensors comprise at least one microphone.
 37. Thesystem of claim 31, wherein the implantable system further comprises arespiratory sensor to sense a respiratory signal indicative ofrespiratory cycles each including an inspiratory phase and expiratoryphase, wherein the heart sound measurement module is adapted to measurethe one or more parameters during the expiratory phase.
 38. The systemof claim 37, wherein the respiratory sensor comprises a minuteventilation impedance sensor incorporated onto the implantable medicaldevice.
 39. The system of claim 37, wherein the respiratory sensorcomprises an accelerometer incorporated onto the implantable medicaldevice.
 40. The system of claim 31, wherein the external systemcomprises a patient monitoring system including: an external devicecommunicatively coupled to the implantable medical device via telemetry;a telecommunication network coupled to the external device; and a remotedevice, coupled to the telecommunication network, to allow communicationwith the implantable medical device from a remote location.
 41. Thesystem of claim 40, wherein the heart sound morphology analyzer isincluded in the remote device.
 42. The system of claim 41, wherein theexternal controller further comprise a pacing parameter optimizationmodule adapted to optimize one or more pacing parameters based on the atleast the dyssynchrony parameter.
 43. The system of claim 42, whereinthe implantable medical device comprises a cardiac resynchronizationtherapy (CRT) device.
 44. A method for operating a cardiac pacemaker,comprising: receiving one or more heart sound signals indicative ofheart sounds of at least one predetermined type; detecting the heartsounds of the at least one predetermined type; producing one or moredyssynchrony parameters each indicative of a degree of cardiacmechanical dyssynchrony based on at least one morphological feature ofthe detected heart sounds of the at least one predetermined type byexecuting an automated cardiac mechanical dyssynchrony algorithm; anddetermining one or more pacing parameters for minimizing the degree ofcardiac mechanical dyssynchrony based on the one or more dyssynchronyparameters.
 45. The method of claim 44, further comprising sensing theone or more heart sound signals using one or more implantable heartsound sensors.
 46. The method of claim 45, wherein sensing the one ormore heart sound signals comprises sensing one or more heart soundsignals each indicative of at least first heart sounds (S1) and secondheart sounds (S2).
 47. The method of claim 46, wherein sensing the oneor more heart sound signals comprises sensing one or more accelerationsignals.
 48. The method of claim 46, wherein sensing the one or moreheart sound signals comprises sensing one or more audio signals usingone or more microphones.
 49. The method of claim 46, wherein sensing theone or more heart sound signals comprises sensing a first heart soundsignal from a right ventricle (RV) and sensing a second heart soundsignal from a left ventricle (LV).
 50. The method of claim 46, furthercomprising: producing an envelope of each of the one or more heart soundsignals by rectifying and low-pass filtering the each of the one or moreheart sound signals; and ensemble averaging each of the one or moreheart sound signals to improve a signal-to-noise ratio of the each ofthe one or more heart sound signals.
 51. The method of claim 46, whereinproducing the one or more dyssynchrony parameters comprises producing afirst dyssynchrony parameter related to S1 and producing a seconddyssynchrony parameter related to S2.
 52. The method of claim 51,further comprising: receiving a respiratory signal indicative ofrespiratory cycles each including an inspiratory phase and expiratoryphase; and detecting the expiratory phase, wherein producing the seconddyssynchrony parameter related to S2 comprises producing the seconddyssynchrony parameter related to S2 based on at least one morphologicalfeature of S2 detected during the expiratory phase.
 53. The method ofclaim 52, further comprising sensing the respiratory signal by sensingan thoracic impedance signal indicative minute ventilation.
 54. Themethod of claim 52, further comprising sensing the respiratory signal bysensing an acceleration signal indicative of inspiration and expiration.55. The method of claim 51, wherein producing the first dyssynebronyparameter related to S1 comprises measuring an S1 width, and producingthe second dyssynchrony parameter related to S2 comprises measuring anS2 width.
 56. The method of claim 51, wherein producing the firstdyssynchrony parameter related to S1 comprises measuring an S1 delayrepresenting a time interval between a tricuspid valve closure and amitral valve closure during one cardiac cycle, and producing the seconddyssynchrony parameter related to S2 comprises measuring an S2 delayrepresenting delay between a pulmonary valve closure and an aortic valveclosure during one cardiac cycle.
 57. The method of claim 51, whereinproducing the first dyssyncbrony parameter related to S1 comprisesproducing a time-frequency representation of S1 and producing a firstdyssynchrony parameter associated with at least one feature in thetime-frequency representation of S1, and producing the firstdyssynchrony parameter related to S2 comprises producing atime-frequency representation of S2 and producing a second dyssynchronyparameter associated with at least one feature in the time-frequencyrepresentation of S2.
 58. The method of claim 57, further comprisingproducing a parameter indicative of pulmonary artery pressure based onat least the time-frequency representation of S2.
 59. The method ofclaim 57, wherein producing the time-frequency representation of S1 andthe time-frequency representation of S2 each comprise performing ashort-time Fourier transform (STFT).
 60. The method of claim 57, whereinproducing the time-frequency representation of S1 and the time-frequencyrepresentation of S2 each comprise performing a reduced interference(RID).
 61. The method of claim 57, wherein producing the time-frequencyrepresentation of S1 and the time-frequency representation of S2 eachcomprise performing a wavelet transform (WT).
 62. The method of claim51, wherein determining the one or more pacing parameters comprisesoptimizing the one or more pacing parameters based on at least thesecond dyssynchrony parameter.
 63. The method of claim 62, whereindetermining the one or more pacing parameters further comprisesoptimizing the one or more pacing parameters based on the firstdyssynchrony parameter.
 64. The method of claim 63, further comprisingdelivering pacing pulses using the one or more pacing parameters. 65.The method of claim 44, wherein determining the one or more pacingparameters comprises adjusting the one or more pacing parameters for anapproximately optimal value of each of the one or more dyssynchronyparameters, the approximately optimal value being a value associatedwith an approximately minimum degree of cardiac mechanical dyssynchronyobtained by the adjusting the one or more pacing parameters.
 66. Themethod of claim 65, wherein adjusting the one or more pacing parameterscomprises selecting one or more pacing sites to which the pacing pulsesare delivered.
 67. The method of claim 65, wherein adjusting the one ormore pacing parameters comprises adjusting one or more atrioventriculardelays (AVDs) at which ventricular pacing pulses are delivered.
 68. Themethod of claim 65, wherein adjusting the one or more pacing parameterscomprises adjusting one or more interventricular delays (IVDs) at whichventricular pacing pulses are delivered.
 69. The method of claim 44,wherein determining the one or more pacing parameters comprises:generating a plurality of pacing parameter sets each including one ormore adjustable pacing parameters; delivering a plurality of the pacingpulse sequences each including a plurality of pacing pulses deliveredusing one pacing parameter set of the plurality of pacing parametersets; associating each pacing parameter set of the plurality of pacingparameter sets to a value of at least one of the one or moredyssynchrony parameters; and selecting an optimal parameter set of theplurality of parameter sets, the optimal parameter set associated withan optimal value of at least one of the one or more dyssynchronyparameters, the optimal value associated with a minimum degree ofcardiac mechanical dyssynchrony.
 70. The method of claim 69, whereingenerating the plurality of pacing parameter sets comprises generating aplurality of pacing sites to one or more of which the pacing pulses aredelivered.
 71. The method of claim 69, wherein generating the pluralityof pacing parameter sets comprises generating a plurality ofatrioventricular delays (AVDs) at which ventricular pacing pulses aredelivered.
 72. The method of claim 69, wherein generating the pluralityof pacing parameter sets comprises generating a plurality ofinterventricular delays (IVDs) at which ventricular pacing pulses aredelivered.